Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations.,Chemical Communications

当前位置： X-MOL 学术 › Chem. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations.
Chemical Communications ( IF 4.3 ) Pub Date : 2020-06-30 , DOI: 10.1039/d0cc03558k
Piero Procacci ₁ , Marina Macchiagodena ₁ , Marco Pagliai ₁ , Guido Guarnieri ₂ , Francesco Iannone ₂

Affiliation

Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PL^pro, 3CL^pro, RdRp. By analyzing the bound state configurations, we were able to improve the potency for the 3CL^pro target, designing a novel HCQ-inspired compound, named PMP329, with predicted nanomolar activity. If confirmed in vitro, our results provide a molecular rationale for the use of HCQ or of strictly related derivatives in the treatment of Covid-19.

中文翻译：

羟基氯喹与SARS-CoV2功能蛋白的相互作用，采用全原子非平衡炼金术模拟。

结合使用增强的采样分子动力学技术和具有完整原子细节的非平衡炼金术转化，我们证明了羟氯喹（HCQ）可能作为SARS-CoV2复制中重要功能蛋白的温和抑制剂，其功效在系列中有所增加PL^专业版，3CL^专业版，RdRp。通过分析结合态构型，我们能够提高3CL ^pro靶的效价，设计了一种新型的HCQ激发化合物，名为PMP329，具有预测的纳摩尔活性。如果在体外得到证实，我们的结果将为使用HCQ或严格相关的衍生物治疗Covid-19提供分子原理。

更新日期：2020-08-04

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11